We plan to test the calcium hypothesis of phototransduction by using the pressure-injection/voltage clamp technique. We will inject solutions containing a known free calcium concentration (buffered with EGTA or other calcium chelators; see Lisman and Brown, 1975; Meech, 1974). These experiments will allow us to determine the range of (Ca plus2)i that is effective in modulating gNa. In addition steady background lights, which have been suggested to alter (Ca plus2)i lipton, Ostroy, and Dowling, 1977; Flaming and Brown, 1979), will be used. If (Ca plus2)i is increased by a background, then the magnitude of the EGTA-induced change in slope resistance should be increased. We also plan to use the pressure-injection/voltage clamp technique to investigate the role of cyclic nucleotides as intracellular messengers for excitation. Cyclic guanosine monophosphate (cGMP) has been suggested to modulate gNa in the plasma membrane of the rod outer segment (see Miller and Nicol, 1979, for a summary). It is possible that both Ca plus2 and cGMP are intracellular messengers (see Lipton, Rasmussen, and Dowling, 1977). We plan to inject cGMP alone, as well as cGMP in solutions with known (buffered) free calcium concentrations. It is hoped that these experiments will begin to define the relative roles of Ca plus2 and cGMP in the transduction process in rod photoreceptors.